title: VWF attributes--impact on thrombus formation.
abstract: At sites of vascular injury, free-flowing platelets attach to the vessel wall to initiate thrombus formation in areas of high haemodynamic shear stress, a process that is critical for both haemostasis and thrombosis. This reaction is mediated by the binding of the platelet glycoprotein (GP) Iba to the A1 domain of immobilized von Willebrand factor (VWF), resulting in a complex series of events that includes platelet adhesion, activation and aggregation. Under elevated rates of shear stress these events support the formation of platelet-derived tethers and microparticles (MPs), which contain adhesive receptors and glycoproteins, and can bind to immobilized and soluble VWF, thereby facilitating thrombus formation. Understanding of the unique functional attributes of VWF has helped elucidate the interaction between VWF and platelets and its subsequent impact on thrombus formation. This interaction is multifaceted and modulated by different environmental conditions. A novel mechanism for initiating thrombus formation under high haemodynamic forces has recently been demonstrated. Results from direct real-time visualization of blood flow studies demonstrate activation-independent platelet aggregation, which occurs exclusively through binding of soluble VWF to platelet GPIb at very high shear stress, and may thus contribute to acute thrombotic occlusion. This article reviews the attributes of VWF and their impact on thrombus formation.
authors.affiliation: Department of Transfusion Medicine and Haemostaseology, Clinic for Anaesthesiology, University Clinic Munich, Max-Lebsche-Platz 32, Munich, Germany. Armin.Reininger@med.uni-muenchen.de
authors.forename: Armin J
authors.initials: AJ
authors.lastname: Reininger
mesh_terms: D006801:Humans; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D011487:Protein Conformation; D033081:Shear Strength; D013927:Thrombosis / Q000209:etiology*; D014841:von Willebrand Factor / Q000737:chemistry / Q000502:physiology*
chemical_list: D014841:von Willebrand Factor